Herpesviruses have developed strategies to counteract host defenses so as to allow viruses to infect cells and result in a latent or persistent infection. The goal of this project is to identify and determine the function of herpesvirus proteins that interact with host cell proteins to influence the course of infection. These proteins may allow us to identify new molecules that are important in the human immune system.Epstein-Barr virus (EBV) infects B lymphocytes, causes infectious mononucleosis, and is associated with certain human tumors. Recently we have found that a protein encoded by the Epstein-Barr virus (BARF1) encodes a soluble receptor for a cytokine and inhibits secretion of interferon-alpha. This may allow the virus to persist in the body despite a vigorous immune response. Programmed cell death (apoptosis) is an antiviral defense mechanism used by the host to eliminate virus-infected cells. Some viruses encode proteins that interfere with signaling pathways for apoptosis. We have identified two families of proteins encoded by DNA viruses, that modulate programmed cell death. One of these families encodes the homolog of a cellular protein that inhibits programmed cell death, while the other viral protein is the homolog of a cellular protein that induces cell death. We have shown that several of the viral proteins have similar activities as the cellular proteins, and that the viral proteins bind to other cellular proteins that normally mediate apoptosis - Apoptosis, cytokines, interferon, Epstein-Barr Virus, herpesviruses, poxvirus